High Expression of Nucleotide-binding Oligomerization Domain Protein 1 Correlates with Poor Prognosis and Immune Cell Infiltration in Glioblastoma Multiforme Patients

Overview

Journal Discov Oncol

Publisher Springer

Date 2025 Jan 11

PMID 39798050

Authors

Hongyang Zhao

Beiwu Lan

Zenghui Zhao

Peining Zhu

Chong Wang

Yufei Gao

Affiliations

Soon will be listed here.

Abstract

Nucleotide-binding oligomerization domain protein 1 (NOD1) is one of the innate immune receptors that has been associated with tumorigenesis and abnormally expressed in various cancers. However, the role of NOD1 in Glioblastoma Multiforme (GBM) has not been investigated. We used the Tumor Immune Estimate Resource (TIMER) database to compare the differential expression of NOD1 in various tumors. NOD1 expression in GBM was further validated in the GEO database, and the survival of NOD1 was assessed by the Kaplan-Meier method. Clinical samples were collected to validate NOD1 expression. GSEA was carried out to expound on NOD1-related pathways involved in GBM. NOD1 co-expression and enrichment analysis were performed using the Linked Omics database and R software. The relationship between immune infiltrates and NOD1 expression was assessed by TIMER. Besides, the correlation between NOD1 and immune signatures (immunomodulators and chemokine) was evaluated by TISIDB. We found that NOD1 expression was significantly upregulated in GBM patients, and higher expression of NOD1 was associated with a poor prognosis. GSEA and enrichment analysis revealed that NOD1 might play a vital role in immune response and GBM progression. TIMER analysis showed a positive correlation between NOD1 expression and 17 types of tumor-infiltrating immune cells. Moreover, NOD1 expression was positively correlated with the expression of chemokine and immunomodulators in GBM. Overall, our findings suggest that NOD1 is a promising prognostic biomarker and is associated with immune cell infiltration in GBM, making it a potential diagnostic biomarker for this aggressive brain cancer.

References

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

Mukherjee T, Hovingh E, Foerster E, Abdel-Nour M, Philpott D, Girardin S . NOD1 and NOD2 in inflammation, immunity and disease. Arch Biochem Biophys. 2018; 670:69-81. DOI: 10.1016/j.abb.2018.12.022. View

Russo G, Musso N, Romano A, Caruso G, Petralia S, Lanzano L . The Role of Dielectrophoresis for Cancer Diagnosis and Prognosis. Cancers (Basel). 2022; 14(1). PMC: 8750463. DOI: 10.3390/cancers14010198. View

Bouskra D, Brezillon C, Berard M, Werts C, Varona R, Gomperts Boneca I . Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature. 2008; 456(7221):507-10. DOI: 10.1038/nature07450. View

Guo X, Li X, Zhou P, Li D, Lyu X, Chen Y . Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway. Int J Mol Sci. 2018; 19(11). PMC: 6274686. DOI: 10.3390/ijms19113419. View

Louis D, Ohgaki H, Wiestler O, Cavenee W, Burger P, Jouvet A . The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007; 114(2):97-109. PMC: 1929165. DOI: 10.1007/s00401-007-0243-4. View

Minaga K, Watanabe T, Kamata K, Asano N, Kudo M . Nucleotide-binding oligomerization domain 1 and infection: A review. World J Gastroenterol. 2018; 24(16):1725-1733. PMC: 5922992. DOI: 10.3748/wjg.v24.i16.1725. View

Furnari F, Fenton T, Bachoo R, Mukasa A, Stommel J, Stegh A . Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007; 21(21):2683-710. DOI: 10.1101/gad.1596707. View

Park J, Kim Y, Shaw M, Kanneganti T, Fujimoto Y, Fukase K . Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells. J Immunol. 2007; 179(1):514-21. DOI: 10.4049/jimmunol.179.1.514. View

Hu B, Wang Q, Wang Y, Hua S, Gabriel Sauve C, Ong D . Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth. Cell. 2016; 167(5):1281-1295.e18. PMC: 5320931. DOI: 10.1016/j.cell.2016.10.039. View

10.

Broggi G, Salvatorelli L, Barbagallo D, Certo F, Altieri R, Tirro E . Diagnostic Utility of the Immunohistochemical Expression of Serine and Arginine Rich Splicing Factor 1 (SRSF1) in the Differential Diagnosis of Adult Gliomas. Cancers (Basel). 2021; 13(9). PMC: 8123436. DOI: 10.3390/cancers13092086. View

11.

Liu X, Ma H, Fei L, Jiang M, Xia M, Bai L . HPV-mediated down-regulation of NOD1 inhibits apoptosis in cervical cancer. Infect Agent Cancer. 2020; 15:6. PMC: 6993450. DOI: 10.1186/s13027-020-0272-3. View

12.

Tsuji Y, Watanabe T, Kudo M, Arai H, Strober W, Chiba T . Sensing of commensal organisms by the intracellular sensor NOD1 mediates experimental pancreatitis. Immunity. 2012; 37(2):326-38. PMC: 3523885. DOI: 10.1016/j.immuni.2012.05.024. View

13.

Weller M, van den Bent M, Hopkins K, Tonn J, Stupp R, Falini A . EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014; 15(9):e395-403. DOI: 10.1016/S1470-2045(14)70011-7. View

14.

Bagchi S, Yuan R, Engleman E . Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance. Annu Rev Pathol. 2020; 16:223-249. DOI: 10.1146/annurev-pathol-042020-042741. View

14.

Xu H, Li X, Adams H, Kubena K, Guo S . Etiology of Metabolic Syndrome and Dietary Intervention. Int J Mol Sci. 2019; 20(1). PMC: 6337367. DOI: 10.3390/ijms20010128. View

15.

Park J, Kim Y, McDonald C, Kanneganti T, Hasegawa M, Body-Malapel M . RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J Immunol. 2007; 178(4):2380-6. DOI: 10.4049/jimmunol.178.4.2380. View

16.

Chen H, Li M, Guo Y, Zhong Y, He Z, Xu Y . Immune response in glioma's microenvironment. Innov Surg Sci. 2021; 5(3-4):20190001. PMC: 7810204. DOI: 10.1515/iss-2019-0001. View

17.

Yoon H, Ahn M, Kwon S, Kim D, Lee J, Yoon J . Nucleotide-binding oligomerization domain 2 (NOD2) activation induces apoptosis of human oral squamous cell carcinoma cells. J Oral Pathol Med. 2015; 45(4):262-7. DOI: 10.1111/jop.12354. View

18.

Galluzzi L, Humeau J, Buque A, Zitvogel L, Kroemer G . Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol. 2020; 17(12):725-741. DOI: 10.1038/s41571-020-0413-z. View